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Epilepsia. 2004 May;45(5):436-40.

Valproate reduced synaptic activity increase induced by 4-aminopyridine at the hippocampal CA3-CA1 synapse.

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Brain Mapping Unit, Pluridisciplinary Institute, UCM, Madrid, Spain.



We investigated the effects of valproate (VPA) on excitatory synaptic transmission changes induced by 4-aminopyridine (4-AP) to determine whether the antiepileptic effects shown by VPA can be ascribed to a modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in the CA3-CA1 synapse.


Rat hippocampal slices were prepared and maintained in vitro with standard methods. Whole-cell current and voltage-clamp recordings were obtained from CA1 pyramidal neurons by using the "blind" patch-clamp technique in an immersion recording chamber. Increase in the spontaneous excitatory synaptic activity was induced by addition of 4-AP to the medium.


Perfusion with VPA significantly counteracted the increase of frequency and amplitude of the sEPSCs induced by application of 4-AP and suppressed the epileptiform activity.


We conclude that VPA decreases the 4-AP-induced enhancement of excitatory synaptic activity at the CA3-CA1 synapse, and that this reduction of excitation input to CA1 contributes to the anticonvulsant effects of VPA.

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